Clinical consequences of a polygenic predisposition to benign lower white blood cell counts
Year: 2023
Type: preprint
Study design: Observational Study
Abstract: ABSTRACT Polygenic variation unrelated to disease contributes to interindividual variation in baseline white blood cell (WBC) counts, but its clinical significance is undefined. We investigated the clinical consequences of a genetic predisposition toward lower WBC counts among 89,559 biobank participants from tertiary care centers using a polygenic score for WBC count (PGS WBC ) comprising single nucleotide polymorphisms not associated with disease. A predisposition to lower WBC counts was associated with a decreased risk of identifying pathology on a bone marrow biopsy performed for a low WBC count (odds-ratio=0.55 per standard deviation increase in PGS WBC [95%CI, 0.30 - 0.94], p=0.04), an increased risk of leukopenia (a low WBC count) when treated with a chemotherapeutic (n=1,724, hazard ratio [HR]=0.78 [0.69 - 0.88], p=4.0×10 -5 ) or immunosuppressant (n=354, HR=0.61 [0.38 – 0.99], p=0.04). A predisposition to benign lower WBC counts was associated with an increased risk of discontinuing azathioprine treatment (n=1,466, HR=0.62 [0.44 - 0.87], p=0.006). Collectively, these findings suggest that a WBC count polygenic score identifies individuals who are susceptible to escalations or alterations in clinical care that may be harmful or of little benefit.
Source: medRxiv
Authors: Jonathan D. Mosley, John P. Shelley, Alyson L. Dickson, Jacy Zanussi, Laura L. Daniel, Neil S. Zheng, Lisa Bastarache, Wei-Qi Wei, Mingjian Shi, Gail P. Jarvik, Elisabeth A. Rosenthal, Atlas Khan, Alborz Sherafati, Iftikhar J. Kullo, Theresa L. Walunas, Joe Glessner, Hakon Hakonarson, Nancy J. Cox, Dan M. Roden, Stephan G. Frangakis, Brett Vanderwerff, C. Michael Stein, Sara L. Van Driest, Scott C. Borinstein, Xiao-Ou Shu, Matthew Zawistowski, Cecilia P. Chung, Vivian K. Kawai
Institutions: Vanderbilt University Medical Center, Yale University, University of Washington, University of Washington Medical Center, Columbia University, Mayo Clinic, Northwestern University, Children's Hospital of Philadelphia, University of Pennsylvania, Vanderbilt University, University of Michigan, Michigan Medicine, Vanderbilt-Ingram Cancer Center
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: Children's Hospital of Philadelphia, Vanderbilt University, Northwestern University, Cincinnati Children's Hospital Medical Center, University of Washington, Vanderbilt University Medical Center, Broad Institute, Georgia Clinical and Translational Science Alliance, National Institutes of Health, National Human Genome Research Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, Division of Materials Research, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1085576015, EHR-based Genomic Discovery and Implementation, G1531600799, G1678063915, G1766209448, G2103760183, Understanding the genetic risk underlying racial disparities in uterine fibroids, G2615776415, G2683268942, G2822312608, G2888548701, G2944859474, G303142226, G3395468139, G3619590958, G364208108, G3724712001, G3791753988, Medical Scientist Training Program, G3938985443, G4049315607, G4203491109, Automated Storage and Retrieval of Biological Systems, G4324164867, G4395870004, G4410787187, G5006584880, G5125508312, G560889077, G5679716143, G5717004637, Genetic Epidemiology of Multiple Sclerosis, G6071621673, Genetic Discovery and Application in a Clinical Setting Continuing a Partnership, G635500700, G6589054092, G6771882875, G6975713648, G7163342664, G7168644870, G7566532274, Genome and Phenome to Define Disease Risk with Antinuclear Antibodies, The Vanderbilt Institute for Clinical and Translational Research (VICTR), Pharmacogenetics to improve drug therapy, G8098630230, Epidemiologic Architecture for Genes Linked to Environment (EAGLE), G8332127685, G8565821944, G9000000364, G9000007771, G9000008449, G9000022508, G9000022789, G9000031451, G9000043901, G9000054231, G9000074171, G9000083610, G9000090229, G9000134904, G9000167145, G9000168329, G9000169515, G9000212326, G9000217501, G9000270828, Genetic Markers of Chronic Postsurgical Pain, G95160140
OpenAlex ID: W4386021025